Pharmacological aspects of the neuroprotective effects of irreversible MAO-B inhibitors, selegiline and rasagiline, in Parkinson’s disease

TLDR: The era of MAO-B inhibitors dates back more than 50 years and began with Kálmán Magyar’s outstanding discovery of the selective inhibitor, selegiline, which is still regarded as the gold standard, although newer drugs have also been introduced to the field.

Abstract: The era of MAO-B inhibitors dates back more than 50 years It began with Kalman Magyar’s outstanding discovery of the selective inhibitor, selegiline This compound is still regarded as the gold standard of MAO-B inhibition, although newer drugs have also been introduced to the field It was revealed early on that selective, even irreversible inhibition of MAO-B is free from the severe side effect of the non-selective MAO inhibitors, the potentiation of tyramine, resulting in the so-called ‘cheese effect’ Since MAO-B is involved mainly in the degradation of dopamine, the inhibitors lack any antidepressant effect; however, they became first-line medications for the therapy of Parkinson’s disease based on their dopamine-sparing activity Extensive studies with selegiline indicated its complex pharmacological activity profile with MAO-B-independent mechanisms involved Some of these beneficial effects, such as neuroprotective and antiapoptotic properties, were connected to its propargylamine structure The second MAO-B inhibitor approved for the treatment of Parkinson’s disease, rasagiline also possesses this structural element and shows similar pharmacological characteristics The preclinical studies performed with selegiline and rasagiline are summarized in this review